Potential of gelatin hydrogel nonwoven fabrics (Genocel) as a skin substitute in a diabetic mouse skin defect model.

Background: Gelatin hydrogel nonwoven fabrics (Genocel) are three-dimensional gelatin scaffolds that provide cells with space for proliferation, migration, and differentiation. They are expected to be an effective wound healing modality to treat intractable wounds, such as diabetic foot ulcers, because they enhance early neovascularization when used as a skin substitute. In this study, we explored the healing process of Genocel applied to skin defects in diabetic mice and compared it with that of a conventional skin substitute, Pelnac. Methods: Genocel and Pelnac sheets were used to treat skin defects on the backs of diabetic mice. On days 7 and 14, the remaining wound area was evaluated and specimens were harvested for HE, Azan, anti-CD31, CD68, and CD163 staining to assess neoepithelialization, granulation tissue formation, capillary formation, and macrophage infiltration. Results: Wounds treated with Genocel showed a wound healing process comparable to that of wounds treated with Pelnac. No significant differences were observed in the remaining wound area, neoepithelial length, granulation formation, number of pan-macrophages, or M2 ratio on days 7 and 14. The only significant difference was the number of induced M2 macrophages, which was higher in Pelnac group than in the Genocel group on day 7 (p < 0.05). Conclusions: Genocel showed similar healing effects in diabetic wounds as Pelnac and is considered an effective wound management modality for diabetic ulcers.

Repeated Fluid Accumulation around a Breast Implant Related to Synovial Metaplasia of the Capsule.

We must take special care when treating postoperative fluid accumulation around breast implants (BIs) to exclude any serious complications, including BI-associated anaplastic large cell lymphoma. However, most late-onset fluid accumulation is caused by other conditions, such as traumatic hematoma and residual postoperative seroma. Surgeons must choose whether to conservatively observe or remove such BIs, while also determining whether to perform partial capsulectomy or total capsulectomy to solve the problem of fluid accumulation. We treated a 72-year-old woman who noticed swelling in her right breast 4 years after undergoing bilateral BI reconstruction. Before she was referred to our hospital, the fluid had been drained by needle aspiration five times, but the swelling returned to a similar size within a month. No malignant findings were observed by needle-aspirated cytology or flow cytometry. The patient requested the simultaneous removal of the left BI. Therefore, we performed both BI removal with total capsulectomy on the right side and partial capsulectomy of the superficial layer on the left side. A pathological examination of the capsule on the right side indicated a chronic expanding hematoma and synovial metaplasia characterized by papillary projections rich in CD68-positive cells, thus indicating reactive synovial cells. In contrast, the left superficial capsule was much thinner and showed less synovial metaplasia. Our findings indicate the advantages of total capsulectomy to solve the problem of repeated serous fluid accumulation around BIs, according to histological changes in the capsule.

Multivariate Analysis of Risk Factors for Complications in Pediatric Tissue Expansion.

BACKGROUND: Tissue expanders represent one of the main surgical options for skin reconstruction in cases of tumors, traumalike burn injury, scar contracture, and alopecia. However, the tissue expander device is also associated with complications such as infection and extrusion. The aim of this study was to analyze risk factors for major complications of use of tissue expanders in pediatric patients using multivariate analysis. METHODS: A retrospective, single-center observational study was performed over 10 years in pediatric patients who were treated with tissue expanders for tumors, nevus, scars, burn reconstruction, and alopecia from April 2012 to March 2022. The primary outcome was overall complications per operation and expander, including infection and extrusion. Ten predictor variables were included as risk factors based on previous studies and as new factors considered important from clinical experience. Univariate and multivariate logistic regression analyses were performed to identify risk factors for major complications such as expander infection or extrusion. RESULTS: The study included 44 patients who underwent 92 operations using 238 tissue expanders. The overall complication rate per expander was 14.3%. Univariate logistic regression analysis identified associations of younger age, number of expanders used per operation, history of infection, and tissue expander locations with a higher complication rate. In multivariate logistic regression analysis, younger age (odds ratio, 1.14; P = 0.043) was associated with a high likelihood of expander complications. CONCLUSIONS: Younger age is an independent risk factor for tissue expander complications in pediatric patients. This factor should be considered in preoperative planning and discussions with the patient's family.

Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi.

Neurocutaneous melanosis (NCM) is a rare, non-hereditary neurocutaneous disorder characterized by excessive melanocytic proliferation in the skin and central nervous system. As no major studies have covered the incidence of NCM among Japanese patients with congenital melanocytic nevi (CMN), we prospectively investigated the incidence of NCM among Japanese patients who underwent initial treatment for CMN. The relationship of CMN and NCM was also investigated. Japanese pediatric patients with CMN under 1 year of age were included between January 2020 and November 2022, and all patients underwent brain MRI to check for NCM in this study. NCM lesions were most frequently seen in the amygdala, followed by the cerebellum, brainstem, and cerebral hemispheres. NCM was diagnosed on brain MRI in 31.6% of the 38 patients with CMN and in 25.0% of patients with no prior examination or treatment. Distribution and size of CMN, number of satellite nevi, rugosity and nodules were strongly associated with the existence of NCM, and these findings may guide a future registry study with a large cohort of CMN patients.

Comparisons of the effects of silk elastin and collagen sponges on wound healing in murine models.

Introductions: Silk elastin, a recombinant protein with repeats of elastin and silk fibroin, possesses a self-gelling ability and is a potential wound dressing material. The aim of this study is to elucidate the mechanism of the wound healing-promoting effect of silk elastin by comparing its in vivo behavior in a mouse wound model with that of a collagen sponge. Methods: Skin defects (8 mm in diameter) were created on the backs of C57BL/6J and BKS.Cg- + Lepr/+Lepr db male mice. Silk elastin sponges of 2.5 or 5.0 mm thickness, as well as collagen sponges, were placed on the wounds and secured with a polyurethane film. In the control group, only the polyurethane film was applied. The remaining wound area was grossly evaluated, and tissue samples were collected after 7, 14, and 21 days for histological evaluation, including neoepithelialization, wound contraction, granulation tissue formation, newly formed capillaries, and macrophages. Genetic analysis was conducted using real-time polymerase chain reaction. Results: In the study with C57BL/6J, there were no significant differences between the silk elastin and collagen sponge groups. Similarly, in the study using BKS.Cg- + Lepr/+Lepr db, no significant differences were found in the remaining wound area and granulation tissue formation between the silk elastin and collagen sponge groups. However, on day 14, the 5.0-mm-thick silk elastin sponge group showed increased macrophages, longer neoepithelialization, and more frequent angiogenesis compared to other groups. Gene expression of inducible nitric oxide synthase and arginase-1 was also higher in the 5.0 mm thick silk elastin sponge group. Conclusions: Silk elastin sponges demonstrated superior neoepithelialization and angiogenesis compared to collagen sponges. The results suggest that silk elastin and collagen sponges promote wound healing through different mechanisms, with silk elastin possibly enhancing wound healing by facilitating increased macrophage migration. Further studies are needed, but silk elastin shows great potential as a versatile wound dressing material.

Flap Viability Evaluation Using a Tissue Oximetry Camera as an Alternative to Indocyanine Green Fluorescence Imaging.

Indocyanine green (ICG) fluorescence imaging is useful for assessing flap viability; however, it is associated with a risk of anaphylactic shock, even in patients with no history of drug allergies. SnapshotNIR is a noncontact, camera-type handheld tissue oximeter that can measure the tissue oxygen saturation of the body surface. The device emits red and near infrared light wavelengths and then optimizes the measurement of the differential reflectance from oxygenated and deoxygenated hemoglobin, and StO2 is calculated. A 20 × 15 cm surgical field can be evaluated in less than 3 seconds by holding the camera at a distance of 30 cm. We applied this device at zone II in a deep inferior epigastric perforator (DIEP) flap, and compared the findings with the border of flap perfusion detected by ICG imaging. Left breast reconstruction using a free DIEP flap was performed for a 60-year-old woman. The DIEP flap was vascularized by a perforator vessel coursing to the right abdominis muscle. First, Diagnogreen (5 mg; Daiichi Sankyo Co., Tokyo, Japan) was intravenously injected, and the ICG fluorescence perfusion border detected by PDE-neo (Hamamatsu Photonics, Hamamatsu City, Shizuoka, Japan) was determined. The ICG border was defined by two reconstructive surgeons after fluorescence had spread out for 2 minutes. Next, zones Ⅱ and Ⅳ of the DIEP flap, contralateral to the perforator, were evaluated using photographs obtained by SnapshotNIR. There were significant StO2 value differences between the ICG-negative area and ICG-positive area. This device can be widely applied in the noninvasive evaluation of flap viability.

Interposition grafting of collagen-gelatin sponge impregnated with basic fibroblast growth factor in primary palatoplasty.

Introduction: An oronasal fistula is a challenging post-operative complication of palatoplasty due to impaired velopharyngeal function or its high recurrence rate. Muscle repositioning, a key procedure in palatoplasty, causes dead space at the junction between the hard and soft palates. Consequently, thin oral and nasal mucosae are prone to break down and form fistulas. In this study, we used basic fibroblast growth factor-impregnated collagen gelatin sponge (bFGF-CGS) in primary palatoplasty to reduce fistula formation. Methods: This retrospective study assessed the complications and efficacy of bFGF-CGS to reduce fistula formation. Patients who underwent primary palatoplasty with bFGF-CGS were included. The same number of patients who underwent primary palatoplasty without bFGF-CGS was included as a control group. The outcomes included post-operative oronasal fistula formation, delayed healing, bleeding, and infection. Results: Both groups included 44 patients. Except for age at palatoplasty, there were no statistically significant demographic differences between the two groups; however, the rates of fistula formation in the study and control group were 2.3% and 13.6%, respectively. There were no infections among the patients. Conclusions: The grafting of bFGF-CGS in primary palatoplasty was safe and probably effective in reducing post-operative oronasal fistula formation.

An easy-to-use semi-automatic volumetric evaluation for secondary bone grafting in patients with unilateral alveolar cleft.

Surgical intervention for alveolar bone formation is important in patients with alveolar cleft; however, the treatment methods and materials are still controversial. A precise evaluation method for postoperative bone formation is important for comparing outcomes and establishing the best treatment protocol. The purpose of this study is to establish a new method of evaluating surgical outcomes for patients with alveolar cleft. Computed tomography datasets from 20 patients who underwent secondary alveolar bone grafting were obtained before and 1 year after surgery. Six anatomical landmarks were used to superimpose the preoperative and mirrored preoperative volume and postoperative volume data. The cleft region was segmented by subtracting the preoperative from mirrored preoperative volume data, and the failed osteogenesis region was segmented by subtracting the postoperative volume data from the cleft region; subsequently, the bone formation ratio was calculated. Two observers performed this method using a free software 3D slicer and the average evaluation times were 12.7 and 13.2 min for observers 1 and 2, respectively. Method reliability was determined by evaluating intraclass correlation coefficients. The intra-observer intraclass correlation coefficients were 0.97 and 0.96 for observers 1 and 2, respectively. The inter-observer intraclass correlation coefficient was 0.97. Our method is practical for assessing bone formation after treatment, which does not require specific knowledge or software and can be used by ordinary physicians.

Development of new bioabsorbable implants with de novo adipogenesis.

Poly-L-lactic acid (PLLA) mesh implants containing collagen sponge (CS) were replaced with autologous adipose tissue regeneration in vivo. Herein, we investigated the optimal external frames and internal fillings using poly (lactic-co-ε-caprolactone) (P (LA/CL)), PLLA, and low-molecular-weight PLLA (LMW-PLLA) as the external frame and polyglycolic acid (PGA) nanosheets and CS as the internal filling. We prepared six implants: P (LA/CL) with PGA nano, PLLA with PGA nano, PLLA with CS, PLLA with 1/2 CS, PLLA with 1/4 CS, and LMW-PLLA with CS, and evaluated adipogenesis at 6 and 12 months using a rat inguinal model. The internal spaces in the P (LA/CL) and LMW-PLLA implants collapsed at 6 months, whereas those in the other four implants collapsed at 12 months. Adipose tissue regeneration was not significantly different between the PLLA-implanted groups at 6 and 12 months and was greater than that in the P (LA/CL) with PGA nano and LMW-PLLA with CS groups. The PGA nanosheet inside PLLA was comparable to the CS inside PLLA in the regeneration of adipose tissue and macrophage infiltration. In summary, PLLA is a promising external frame material in which the internal space can be replaced with adipose tissue. Thus, PGA nanosheets are an alternative internal filling material for adipose tissue regeneration.

Long term observation of de novo adipogenesis using novel bioabsorbable implants with larger size in a porcine model.

Introduction: The regeneration of adipose tissue in patients after breast cancer surgery would be desirable without the use of growth factors or cells to avoid potential recurrence and metastasis. We reported that prolate spheroidal-shaped poly-L-lactic acid (PLLA) mesh implants of approximately 18-mm polar diameter and 7.5-mm greatest equatorial diameter containing collagen sponge (CS) would be replaced by regenerated adipose tissue after implantation, thereby suggesting an innovative method for breast reconstruction. Our study aimed to evaluate the adipose tissue regeneration ability of implant aggregates in a porcine model. Methods: We prepared implant aggregates consisting of thirty PLLA mesh implants containing CS packed in a woven poly (glycolic acid) bag. The implant aggregates were inserted under the mammary glands in the porcine abdomen for a year. Single and double groups were classified by inserting either one or two implant aggregates on each side of the abdomen, respectively. Results: In both groups, the volume of the implant aggregates decreased over time, and the formation of adipose tissue peaked between 6 and 9 months. Histologically, the formation of adipose tissue was confirmed in the area that was in contact with native adipose tissue. Conclusions: Our implant aggregates could induce the autologous adipose tissue after long term implantation in vivo, without the use of any growth factor or cell treatment, presenting a potential novel method of breast reconstruction.

Development of a Self-Assembled Dermal Substitute from Human Fibroblasts Using Long-term Three-Dimensional Culture.

Skin substitutes have emerged as an alternative to autografts for the treatment of skin defects. Among them, scaffold-based dermal substitutes have been extensively studied; however, they have certain limitations, such as delayed vascularization, limited elasticity, and the inability to achieve permanent engraftment. Self-assembled, cell-based dermal substitutes are a promising alternative that may overcome these shortcomings but have not yet been developed. In this study, we successfully developed a cell-based dermal substitute (cultured dermis) through the long-term culture of human dermal fibroblasts using the net-mold method, which enables three-dimensional cell culture without the use of a scaffold. Spheroids prepared from human dermal fibroblasts were poured into a net-shaped mold and cultured for 2, 4, or 6 months. The dry weight, tensile strength, collagen and glycosaminoglycan levels, and cell proliferation capacity were assessed and compared among the 2-, 4-, and 6-month culture periods. We found that collagen and glycosaminoglycan levels decreased over time, while the dry weight remained unchanged. Tensile strength increased at 4 months, suggesting that remodeling had progressed. In addition, the cell proliferation capacity was maintained, even after a 6-month culture period. Unexpectedly, the internal part of the cultured dermis became fragile, resulting in the division of the cultured dermis into two collagen-rich tissues, each of which had a thickness of 400 µm and sufficient strength to be sutured during in vivo analysis. The divided 4-month cultured dermis was transplanted to skin defects of immunocompromised mice and its wound healing effects were compared to those of a clinically available collagen-based artificial dermis. The cultured dermis promoted epithelialization and angiogenesis more effectively than the collagen-based artificial dermis. Although further improvements are needed, such as the shortening of the culture period and increasing the size of the cultured dermis, we believe that the cultured dermis presented in this study has the potential to be an innovative material for permanent skin coverage.

A high-hydrostatic pressure device for nevus tissue inactivation and dermal regeneration for reconstructing skin defects after giant congenital melanocytic nevus excision: a clinical trial.

Background: A novel treatment has been developed to reconstruct large skin defects caused by the excision of giant congenital melanocytic nevi. It involves the reimplantation of high-hydrostatic pressurized nevus tissue as a cell-inactivated autologous scaffold for dermal regeneration, followed by the implantation of cultured epithelial autografts on the regenerated dermis. Because this treatment has shown promise in a first-in-human clinical trial which used a prototype pressure machine, a novel pressure device was specifically designed for clinical use. Methods: In a prospective investigator-initiated clinical trial involving three patients, we evaluated the safety and efficacy of the skin regeneration treatment using a pressure device. All three patients underwent surgical excision of the nevus tissue, primary reimplantation of the inactivated nevus tissue, and secondary implantation of cultured epithelial autografts. Results: Engraftment of inactivated nevus tissue and cultured epithelial autografts was successful in all three cases, with over 90% epithelialization at 8 weeks post-surgery. No serious adverse events or device malfunction were observed during the trial. Conclusion: The novel pressure device safely and effectively enabled dermal regeneration using the nevus tissue as an autologous scaffold. This innovative approach offers several advantages, including reduced invasiveness due to minimal sacrifice of normal skin for skin grafting and high curative potential resulting from full-thickness removal of the nevus tissue.

Lower Lip Reconstruction Using a Sensory Anterolateral Thigh Flap as the First Choice.

Local flaps from the upper lip and cheeks have been the first choice for two-thirds to total resection of the lower lip. However, these local flap techniques involve many clinical problems, including small a mouth, drooling, scarring, and hypesthesia. The improvement of free anterolateral thigh (ALT) flap transfer can solve these problems with expansion of the application of free flaps for lower lip reconstruction. The patient in this case was a 56-year-old man with squamous cell carcinoma of the lower lip (cT3N1M0). Subtotal lower lip resection preserving both corners of the mouth with bilateral neck dissection was performed. Simultaneously, a sensory ALT flap was elevated with an 8 × 6 cm skin island and a lateral femoral cutaneous nerve. The lateral and medial sides of the fascia lata were processed into 1-cm-wide strings, which were tunneled through the orbicularis oris muscle of the upper lip and sutured to the orbicularis oris muscle at the mucosal side of the philtrum. The lateral femoral cutaneous nerve and right mental nerve were sutured. At 3 months, a second surgery was performed to replace the ALT flap on the white labial side with a clavicle full-thickness skin graft. This surgery achieved four important factors: opening and closing of the mouth, sensory function of the lower lip, cosmetic appearance, and minimization of donor-site damage. We believe the worldwide improvement of microsurgery techniques enables lower lip reconstruction using the sensory ALT flap to be selected as the first choice for two-thirds to total lower lip defects.

Deep Infantile Hemangioma in the Involuting Phase That Was Difficult to Diagnose before Surgery.

Infantile hemangioma (IH) is a common pediatric vascular tumor and is easily diagnosed in most cases based on the clinical course and appearance, but deep IHs are difficult to diagnose based on external appearance alone. Clinical and imaging findings are therefore important clues to the diagnosis of soft tissue tumors; however, a definitive diagnosis is decided based on the pathological examination of biopsy or resection specimens. A 1-year-old girl with a subcutaneous mass on her glabella was referred to our hospital. At 3 months of age, her mother noticed a tumor that swelled when she cried. It gradually enlarged, and ultrasonography and magnetic resonance imaging were performed at 12 months of age. Doppler ultrasonography showed a hypo-vascular mass. Magnetic resonance imaging revealed a subcutaneous mass with low-intensity on T1-weighted image and slightly high-intensity on T2-weighted image, with tiny flow voids. Computed tomography showed no frontal bone defect. The soft tissue tumor could not be diagnosed based on these imaging findings; thus, we decided to perform total resection under general anesthesia. A histopathological examination showed a highly cellular tumor with capillaries with opened small vascular channels and glucose transporter 1 positivity. Thus, it was diagnosed as deep IH transitioning from the proliferative phase to the involuting phase. Deep IHs are difficult to diagnose because characteristic imaging findings disappear during the involuting phase. We emphasize the importance of performing Doppler ultrasonography in the early phase (eg, at 6 months of age) for soft tissue tumors of infancy.

Modified gelatin hydrogel nonwoven fabrics (Genocel) as a skin substitute in murine skin defects.

Introduction: From previous research, an emerging material composed of gelatin hydrogel nonwoven fabric (Genocel) has shown potential as a skin substitute, by improving neovascularization promotion in the early phase of wound healing. However, Genocel was inferior in terms of granulation formation compared to Pelnac. To solve this problem, we modified the manufacturing process of Genocel to reduce its water content, extend the degradation time (Genocel-L), and evaluate its healing process as a skin substitute. Methods: Genocel with a low water content (Genocel-L) was prepared and the difference in water content compared to that of the conventional Genocel was confirmed. Degradation tests were performed using collagenase and compared among Genocel-L, Genocel, and Pelnac sheets. In the in vivo study, sheets of Genocel-L or Pelnac were applied to skin defects created on the backs of C57BL/6JJcl mice. On days 7, 14, and 21, the remaining wound area was evaluated and specimens were harvested for Hematoxylin and Eosin, Azan, anti-CD31, CD68, and CD163 staining to assess neoepithelialization, granulation tissue, capillary formation, and macrophage infiltration. Results: Genocel-L had a lower water content than the conventional Genocel and a slower degradation than Genocel and Pelnac. In the in vivo experiment, no significant differences were observed between Genocel-L and Pelnac in relation to the wound area, neoepithelium length, granulation formation, and the number of newly formed capillaries. The area of newly formed capillaries in the Pelnac group was significantly larger than that in the Genocel-L group on day 21 (p < 0.05). Regarding macrophage infiltration, significantly more M2 macrophages were induced in the Pelnac group on days 14 and 21, and the M2 ratio was larger in the Pelnac group (p < 0.05) during the entire process. Conclusions: Genocel-L has a lower water content and slower degradation rate than the conventional Genocel. Genocel-L had equivalent efficacy as a skin substitute to Pelnac, and can therefore be considered feasible for use as a skin substitute. However, a manufacturing method that can further modify Genocel-L is required to recover its early angiogenic potential.

Dried human-cultured epidermis accelerates wound healing in a porcine partial-thickness skin defect model.

Introduction: Autologous cultured epidermis (CE) is an effective approach for overcoming the deficiency of donor sites to treat extensive burns. However, the production of autologous CE takes 3-4 weeks, which prevents its use during the life-threatening period of severe burns. In contrast, allogeneic CE can be prepared in advance and used as a wound dressing, releasing several growth factors stimulating the activity of recipient cells at the application site. Dried CE is prepared by drying CEs under controlled temperature and humidity conditions until all the water is completely removed and no viable cells are present. Dried CE accelerates wound healing in a murine skin defect model and is potentially a new therapeutic strategy. However, the dried CE safety and efficacy have not yet been studied in large animal models. Therefore, we studied the safety and efficacy of human-dried CE in wound healing using a miniature swine model. Methods: Human CE was manufactured using Green's method from donor keratinocytes. Three types of CEs (Fresh, Cryopreserved, and Dried) were prepared, and the ability of each CE to promote keratinocyte proliferation was confirmed in vitro. Extracts of the three CEs were added to keratinocytes seeded in 12-well plates, and cell proliferation was evaluated using the WST-8 assay for 7 days. Next, we prepared a partial-thickness skin defect on the back of a miniature swine and applied three types of human CE to evaluate wound healing promotion. On days 4 and 7, the specimens were harvested for hematoxylin-eosin, AZAN, and anti-CD31 staining to assess epithelialization, granulation tissue, and capillary formation. Results: The conditioned medium containing dried CE extract significantly enhanced keratinocyte proliferation compared to the control group (P < 0.05). In vivo experiments revealed that human-dried CE significantly accelerated epithelialization at day 7 to the same extent as fresh CE, compared to the control group (P < 0.05). The three CE groups similarly affected granulation formation and neovascularization. Conclusions: Dried CE accelerated epithelialization in a porcine partial-thickness skin defect model, suggesting that it may be an effective burn treatment alternative. A clinical study with a long-term follow-up is needed to assess the applicability of CEs in clinics.

Development of a novel regenerative therapy for malignant bone tumors using an autograft containing tumor inactivated by high hydrostatic pressurization (HHP).

Surgical resection of malignant bone tumors leads to significant defects in the normal surrounding tissues that should be reconstructed to avoid amputation. Our research aimed to inactivate osteosarcoma (OS)-affected bone to obtain autologous bone grafts for bone defect reconstruction using a novel therapy called high hydrostatic pressurization (HHP) therapy. The key points are complete tumor death and preservation of the non-denatured native extracellular matrix (ECM) and bone tissue by HHP. Previously, we found that HHP at 200 MPa for 10 min can completely inactivate cells in normal skin and skin tumors, including malignant melanoma and squamous cell carcinoma while maintaining their original biochemical properties and biological components. Based on our previous research, this study used HHP at 200 MPa for 10 min to eradicate OS. We prepared an OS cell line (LM8), pressurized it at 200 MPa for 10 min, and confirmed its inactivation through morphological observation, WST-8 assay, and live/dead assay. We then injected OS cells with or without HHP into the bone marrow of the murine tibia, after which we implanted tumor tissues with or without HHP into the anterior surface of the tibia. After HHP, OS cells did not proliferate and were assessed using a live/dead assay. The pressurized cells and tumors did not grow after implantation. The pressurized bone was well prepared as tumor-free autologous bone tissues, resulting in the complete eradication of OS. This straightforward and short-pressing treatment was proven to process the tumor-affected bone to make a transplantable and tumor-free autologous bone substitute.

Development and implementation of a decision aid for post-mastectomy breast reconstruction for Japanese women with breast cancer: a field-testing study.

INTRODUCTION: Surgical options for post-mastectomy breast reconstruction (PMBR) have increased and become more diverse. These options may cause difficulty and stress for patients in making the best choice, and this also increases the likelihood of postoperative regret over a particular decision. To solve this issue, implementation of shared decision-making (SDM) using a decision aid (DA) has become of increasing interest. We have created the first prototype DA in Japan. The aim of the current field study was to assess the usability of this DA in promoting effective SDM and avoiding regret over a decision to undergo reconstructive surgery. METHODS: A total of 25 consecutive patients who underwent BR were enrolled in the study, including 13 with SDM using the decision aid (DA + group) and 12 who received standard information (DA- group) before their choice of surgery. The Decision Regret Scale (DRS) were completed after PMBR, whereas SDM Questionnaire (SDM-Q-9) was completed before PMBR. Descriptive and summary statistics were compared to identify differences between the two groups to assess the usability of the DA. RESULTS: The DA + group had significantly higher mean total scores on the SDM-Q-9 (90.2 ± 5.3 vs. 84.1 ± 3.5, P = 0.0034) and DRS (90.3 ± 3.8 vs. 84.3 ± 6.7, P = 0.023), compared to those in the DA- group. CONCLUSION: Use of the DA may cause patients to have a higher level of perceived SDM and less regret, which suggests that the DA helps to facilitate smooth and effective implementation of SDM. We conclude that this type of decision-making approach should be recommended for choice of surgery for PMBR.

Real-time Navigation for Vascularized Lymph-node Transplantation Using Projection Mapping with Indocyanine Green Fluorescence.

The medical imaging projection system (MIPS) is a real-time surgical navigation device using indocyanine green (ICG) emission signals and active projection mapping. The difference between the object and the projected image is within 1 mm, and the time lag is within 0.1 seconds. We herein report the application of the MIPS to vascularized lymph-node transplantation (VLNT) surgery for lower extremity lymphedema to detect inguinal lymph nodes and perform color-coded navigation surgery for lymph-node resection. A left superficial inguinal lymph node was planned to be used as a donor for VLNT to the right lower leg in a 73-year-old woman with lower extremity lymphedema. Under general anesthesia, multiple intradermal injections of 0.1 ml of ICG were administered around the left inguinal donor site. The MIPS showed a clear linear projection image from a lateral injected point connecting to a lateral superficial inguinal lymph node. The left superficial circumflex iliac artery and vein were dissected for vascularized VLNT. Intraoperative real-time MIPS navigation continuously guided the transection plane colored by ICG fluorescence signals without shifting the visual focus from the surgical field. This is the first report of the intraoperative use of ICG projection mapping for VLNT donor-site surgery. The MIPS was able to visualize functional lymph nodes to facilitate minimally invasive donor-site surgery.

A novel approach for wound treatment using dried cultured epidermal allograft: A phase I/II, single-center, open-label clinical trial.

BACKGROUND: Autologous cultured epidermis (CE) is successfully used in burn care, but it requires a manufacturing time of three weeks and is very expensive owing to its custom-made nature of treatment. To compensate this disadvantage, dried allogeneic CE promises a novel therapeutic approach; and previous reports have demonstrated its efficacy in promoting wound healing using a murine skin defect model. Herein, a prospective clinical study was conducted to confirm the safety and efficacy of dried allogeneic CE for wound treatment. METHODS: Dried CE was manufactured using donor keratinocytes obtained from excess surgical skin and applied to skin defects that were at least 3 cm in length and less than 10 % of the body surface area of the patients. The patients were observed for 14 days after CE application. The primary endpoint was the incidence of adverse events and the secondary endpoint was the percentage of wound healed since baseline, on days 7 and 14. Furthermore, as a stratified analysis, the percentage of wound healed, specified as deep dermal burns, was calculated. RESULTS: Six patients (five burns and one skin ulcer after necrotizing fasciitis) enrolled in the study. As a serious adverse event, a local infection was observed in one patient, which resolved by debridement and conventional skin grafting. Other adverse events that were potentially related to this treatment included two cases of skin erosion, and one case of systemic fever. No unresolved adverse events remained at the end of the study period. The percentage of wound healed was 73.4 ± 19.2 % on Day 7, and 92.2 ± 11.8 % on Day 14. When the targeted disease was restricted to deep dermal burns, the percentage of wound healed was 69.9 ± 28.9 % on Day 7 and 90.5 ± 13.2 % on Day 14. CONCLUSION: Treatment with dried CE was safely performed without any unresolved severe adverse effects. Dried CE is a new and promising modality for skin defect treatment, such as burns and ulcers, and is expected to compensate for the disadvantages of autologous CE. However, large-scale clinical trials are required to confirm their efficacy.